Search Results (219)

The expanded newborn screening (NBS) program in the Russian Federation was initiated in 2023, among which severe combined immunodeficiency (SCID) is screened using TREC/KREC assays. Here, we report a rare case of a TP63-associated disease identified through this NBS program. Dried blood spots from newborns were initially screened for TREC/KREC levels, and those with values below the cut-off underwent confirmatory testing and further genetic analysis, including whole-exome sequencing (WES). A male newborn was identified with significantly reduced TREC values, indicative of T cell lymphopenia. Genetic analysis revealed a heterozygous NM_003722.5:c.1027C>T variant in TP63, leading to the p.(Arg343Trp) substitution within the DNA binding domain. This mutation has been previously associated with Ectrodactyly–Ectodermal Dysplasia–Cleft lip/palate syndrome (EEC) syndrome and shown to reduce the transactivation activity of TP63 in a dominant-negative manner. This case represents one of the few instances of immune system involvement in a patient with a TP63 mutation, highlighting the need for further investigation into the immunological aspects of TP63-associated disorders. Our findings suggest that comprehensive immunological evaluation should be considered for patients with TP63 mutations to better understand and manage potential immune dysfunctions. Full article

Deciding on the implementation or modification of steps in daily clinical care is a nuanced process that demands careful evaluation. This is crucial not only for selecting the most appropriate solution but also for achieving the best treatment outcome. Thus, implementing a workflow for treating cleft lip and/or palate patients with a presurgical orthodontic cleft-covering plate needs to consider objective factors, prioritized from most to least important: safety and quality level, user-friendliness, feasibility, and, finally, efficiency and cost. The goal of this workflow is to integrate CAD/CAM technologies into daily clinical routine to enhance technical and clinical efficiency, reduce the burden of cleft care, and simplify the implementation of these technologies in other facilities. To achieve this, a methodology based on intraoral scanning and additive manufacturing is employed to produce patient-specific passive palatal plates. The approach describes possible pitfalls and their resolution within the routine of a cleft centre, along with an exemplary case scenario. Comparative analysis between the digital workflow and the conventional process demonstrated the digital approach to be safer, higher in quality, more user-friendly, feasible, and cost- and time-effective than the conventional process. Full article

Background: Craniofacial clefts can form a significant defect within bone and cartilage, which can negatively affect tissue homeostasis and the remodeling process. Multiple proteins can affect supportive tissue growth, while also regulating local immune response and tissue protection. Some of these factors, like galectin-10 (Gal-10), nuclear factor kappa-light-chain-enhancer of activated B cells protein 65 (NF-κB p65), heat shock protein 60 (HSP60) and 70 (HSP70) and cathelicidin (LL-37), have not been well studied in cleft-affected supportive tissue, while more known tissue regeneration regulators like type I collagen (Col-I) and bone morphogenetic proteins 2 and 4 (BMP-2/4) have not been assessed jointly with immunomodulation and protective proteins. Information about the presence and interaction of these proteins in cleft-affected supportive tissue could be helpful in developing biomaterials and improving cleft treatment. Methods: Two control groups and two cleft patient groups for bone tissue and cartilage, respectively, were organized with five patients in each group. Immunohistochemistry with the semiquantitative counting method was implemented to determine Gal-10-, NF-κB p65-, HSP60-, HSP70-, LL-37-, Col-I- and BMP-2/4-positive cells within the tissue. Results: Factor-positive cells were identified in each study group. Multiple statistically significant correlations were identified. Conclusions: A significant increase in HSP70-positive chondrocytes in cleft patients could indicate that HSP70 might be reacting to stressors caused by the local tissue defect. A significant increase in Col-I-positive osteocytes in cleft patients might indicate increased bone remodeling and osteocyte activity due to the presence of a cleft. Correlations between factors indicate notable differences in molecular interactions within each group. Full article

Background/Objectives: This study aimed to identify the P-bottle feeding techniques systematically organized by Ms. Kumagai, an expert in nursing care for children with a cleft lip and/or palate (CLP), which were developed as she gained expertise in feeding affected children. Methods: We recruited three nurses who had mastered the Kumagai method for feeding with a P-bottle. Through analysis of participants’ voices and videos during interviews, we focused on aspects such as dealing with a closed mouth, inserting the nipple in cases of unilateral and bilateral CLP, dealing with the child’s movements after insertion, and key considerations when squeezing the bottle. Results: The interview analyses revealed numerous techniques used by nurses to manage the difficulties encountered while feeding children, ensuring successful provision of nourishment. Specifically, the nurses employed techniques such as placing the nipple along the midline of the child’s tongue and varying the application of force on the nipple depending on the cleft type. The nurses reported that the objectives of these techniques were to prevent ulcer formation and encourage the use of the tongue, simulating original feeding movements. Conclusions: We explored feeding techniques and the management of associated challenges. Our results suggest that the “Kumagai Method” could be valuable in improving feeding practices. Full article

Background: This study aims to determine a generalized outcome and risk profile for patients undergoing orthognathic surgery for the definitive treatment of cleft lip and palate. Furthermore, we hope to determine the key risk factors that cause increased risk for cleft lip and palate patients undergoing orthognathic surgery. Methods: This study includes a systematic review using PubMed, MEDLINE, Cochrane, and Scopus. Data curation utilized Covidence software, with dual-reviewer screening and conflict resolution by a third party, focusing on publications with the full texts available. Results: The initial search yielded 1697 articles. Following title, abstract, and full-text screening, a total of 62 articles were included in this review. A total of 70.9% of included articles had moderate bias, with the rest having low risk of bias. The sample consisted of 2550 patients with an average age of about 20 years and an average follow-up of 16.8 months. The most employed procedure was Le Fort I osteotomy (99%). In terms of velopharyngeal function, there were notable increases in insufficiency and severity scores, with an average 63% worsening score from the baseline. That being said, patients experienced an average 33% improvement in speech articulation. Furthermore, the average horizontal movement was reported to be 6.09 mm with a subsequent relapse of 0.98 mm overall. Conclusions: This systematic review distills data from 62 articles and 2550 patients. It highlights the efficacy of orthognathic surgery in addressing oropharyngeal and aesthetic deficits. This study identifies relapse and velopharyngeal insufficiency as recurrent complications. These insights inform surgical refinement and patient counseling, laying a foundation for enhanced clinical protocols. Full article

Background: Bilateral cleft lip palate is a severe congenital birth defect of the mouth and face. Immunity factors modulate immune response, inflammation, and healing; therefore, they are vital in the assessment of the immunological status of the patient. The aim of this study is to assess the distribution of Gal-10, CD-163, IL-4, IL-6, IL-10, HBD-2, HBD-3, and HBD-4 in tissue of the bilateral cleft lip palate in primary dentition children. Methods: Five patients underwent cheiloplasty surgery, where five tissue samples of lip were obtained. Immunohistochemical staining, semi-quantitative evaluation, and non-parametric statistical analysis were used. Results: A statistically significant increase in HBD-2, HBD-3, and HBD-4 was found in skin and mucosal epithelium, hair follicles, and blood vessels. A notable increase was also noted in IL-4, IL-6, and IL-10 in the mucosal epithelium and CD163 in blood vessels. The connective tissue of patients presented with a statistically significant decrease in Gal-10, IL-10, and HBD-3. Spearman’s rank correlation revealed multiple significant positive and negative correlations between the factors. Conclusions: Upregulation of CD163 points to increased angiogenesis but the increase in IL-4 and IL-10 as well as the decrease in Gal-10 points to suppression of excessive inflammatory damage. Decreased connective tissue healing and excessive scarring are suggested by the decrease in HBD-3 and IL-10 and the increase in IL-6. Full article

Background and Objectives: Cleft lip alone or a combination of cleft lip and palate (CLP) is a common developmental abnormality in the craniofacial region. This umbrella review aims to identify promising avenues for treatment using stem cell therapy. Materials and Methods: Systematic reviews from 2014 to 2024 were searched among databases like PubMed, Medline, and Google Scholar. PRISMA guidelines were employed to ensure the thoroughness of the search. A quality assessment (ROBIS) of the included reviews was conducted to ensure the reliability and validity of the synthesized evidence. Results: Five systematic reviews were selected for this umbrella review. Results show that stem cell therapy, specifically using mesenchymal stem cells (MSCs) and adipocyte stem cells (ADSCs), promotes bone regeneration in CLP deformities. Although multiple studies have established the effectiveness of diverse types of stem cells in treating CLP, important considerations including safety concerns, methodological variability, and the need for standardization have been identified. The fact that the number of relevant systematic reviews that matched our inclusion criteria was limited could affect this research’s robustness and may limit the breadth and depth of evidence synthesis. Definitive conclusions could not be reached due to variation among treatments and outcomes. Conclusions: The examined studies highlight the potential of stem cell therapy as a complementary approach to existing treatments for CLP. However, there are challenges that need to be addressed, including concerns regarding safety, variations in methodologies, and the need for standardization. Exploring the potential of other stem cell types may further enhance treatment outcomes for CLP patients. Full article

Cleft lip and/or palate (CL/P) are the most common congenital anomalies in the craniofacial region, leading to morphological and functional disruptions in the facial region. Their etiology involves genetic and environmental factors, with genetics playing a crucial role. This study aimed to investigate the association of four single nucleotide polymorphisms (SNPs)—rs987525, rs590223, rs522616, and rs4714384—with CL/P in the Polish population. We analyzed DNA samples from 209 individuals with CL/P and 418 healthy controls. The impact of SNPs on the presence of CL/P was assessed using multivariate logistic regression. Significant associations were found with rs987525. Specifically, the AC genotype was linked to an increased CL/P risk (odds ratio [OR] = 1.95, 95% confidence interval [CI]: 1.34–2.83, p < 0.001), while the CC genotype was associated with a decreased risk (OR = 0.46, 95% CI: 0.32–0.67, p < 0.001). Rs4714384 was also significant, with the CT genotype correlated with a reduced risk of CL/P (OR = 0.66, 95% CI: 0.46–0.94, p = 0.011). SNPs rs590223 and rs522616 did not show statistically significant associations. These results underscore the role of rs987525 and rs4714384 in influencing CL/P risk and suggest the utility of genetic screening in understanding CL/P etiology. Full article

Comprehensive treatment is crucial for patients with a cleft lip/palate. While studies have investigated its impact on children’s quality of life, few have examined the effects on primary caregivers. The aim of the study was to compare the quality of life of caregivers of children with cleft lip/palate to a control group at the National School for Higher Studies, National Autonomous University of Mexico, Guanajuato. A cross-sectional study was conducted at a teaching dental clinic of the National School of Higher Studies, National Autonomous University of Mexico, Guanajuato, México, from May to December 2021 involving 140 caregivers (70 in each group). The WHOQoL Bref instrument assessed the quality of life. In addition to the descriptive analysis, a binary logistic regression analysis was carried out, taking dichotomized reported quality of life as the dependent variable. Among the caregivers, 88.6% were female (p > 0.05), and 45 (64.8%) from the study group reported poor quality of life (p < 0.05). A multivariate analysis indicated that caring for a child with cleft lip/palate raised the likelihood of poor quality of life (p < 0.05). The findings emphasize the need for comprehensive support for both patients and caregivers, as their well-being affects patient outcomes. Full article

Cleft lip and/or palate are prevalent congenital anomalies. Early and accurate diagnosis allows proper case management. The Objective: This retrospective cohort study aimed to investigate the association between cleft lip and palate and other congenital anomalies. Methods: This study analyzed 17 pregnancies prenatally diagnosed with cleft lip and palate. The investigations consisted of ultrasound examination, fetal karyotyping through amniocentesis, and family tree analysis. In the presence of an abnormal fetal karyotype, the parental karyotype was also indicated. Results: Of the 17 cases identified, 9 (52.94%) were syndromic and 8 (47.06%) were non-syndromic. The genetic syndromes identified in association with cleft lip and palate in this study included translocation syndrome (one case), Patau syndrome, trisomy 13 (seven cases), and Edwards syndrome, mosaic trisomy 18 (one case). Conclusions: A comprehensive approach ensures a thorough assessment and accurate diagnosis. Early detection and a multidisciplinary approach allow appropriate case management. Full article

Background/Objectives: Three-dimensional (3D) analysis of maxillofacial structures in dysmorphic patients offers clinical advantages over 2D analysis due to its high accuracy and precision in measuring many morphological parameters. Currently, no reliable gold standard exists for calculating 3D volumetric measurements of maxillofacial structures when captured by 3D surface imaging techniques. The aim of this scoping review is to provide an overview of the scientific literature related to 3D surface imaging methods used for volumetric analysis of the dysmorphic maxillofacial structures of patients affected by CL/P or other syndromes and to provide an update on the existing protocols, methods, and, when available, reference data. Methods: A total of 17 papers selected according to strict inclusion and exclusion criteria were reviewed for the qualitative analysis out of more than 4500 articles published between 2002 and 2024 that were retrieved from the main electronic scientific databases according to the PRISMA-ScR guidelines. A qualitative synthesis of the protocols used for the selection of the anatomical areas of interest and details on the methods used for the calculation of their volume was completed. Results: The results suggest a great degree of heterogeneity between the reviewed studies in all the aspects analysed (patient population, anatomical structure, area selection, and volume calculation), which prevents any chance of direct comparison between the reported volumetric data. Conclusions: Our qualitative analysis revealed dissimilarities in the procedures specified in the studies, highlighting the need to develop uniform methods and protocols and the need for comparative studies to verify the validity of methods in order to achieve high levels of scientific evidence, homogeneity of volumetric data, and clinical consensus on the methods to use for 3D volumetric surface-based analysis. Full article

Background: Cleft lip and palate is an anomaly that affects both women and men. It is considered to be among the most frequent congenital abnormalities and is related to modifications in chromosomal DNA and multiple genetic alterations. This anomaly can also be associated with various environmental factors, such as tobacco and alcohol consumption, medication use, and exposure to different environmental and industrial toxic substances. The objective of this study was to document the frequency of risk factors related to cleft lip and palate through a systematic review of Mexican studies. Methods: In this systematic review, a bibliographic search was conducted following PRISMA guidelines in the databases Scielo, ScienceDirect, PubMed, and EBSCO. Keywords related to cleft lip and palate, epidemiology, and risk factors were used. In all, 3 independent reviewers (J.A.S.L., S.L.V., and N.M.F.) selected and evaluated a total of 17 articles included in this analysis, achieving a coefficient of κ = 0.84. Results: The analysis revealed that the highest frequency of conducted studies was in the State of Mexico. The most common risk factors identified were environmental, pharmacological, consumption habits, and gynecological factors. Conclusions: Identifying the main risk factors for cleft lip and palate in the Mexican population will enable the implementation of preventive measures aimed at reducing exposure to these factors. Additionally, early intervention can improve the quality of life for individuals affected by this condition. Full article

Background: Morphological differences in the temporomandibular joint (TMJ) are crucial for the treatment of patients with cleft lip and palate (CLP). This study aims to evaluate and compare the TMJ parameters in patients with unilateral and bilateral CLP across growing and non-growing age groups using cone-beam computed tomography (CBCT). Methods: CBCT records from 57 patients (23 males and 34 females) aged 6–50 years with a diagnosed unilateral or bilateral CLP were analyzed. Patients were categorized into four groups: growing unilateral (UGCLP), growing bilateral (BGCLP), non-growing unilateral (UNGCLP), and non-growing bilateral (BNGCLP). Measurements of TMJ parameters, including the mandibular fossa, articular eminence inclination, joint spaces, and roof thickness of the glenoid fossa, were conducted using CBCT images. Results: Significant differences were observed in the anterior joint space (AJS) and the roof of the glenoid fossa (RGF) between growing and non-growing unilateral cleft patients. Additionally, significant discrepancies were found in the articular eminence angle when comparing the cleft and non-cleft sides within the unilateral growing group. No significant differences were observed in TMJ parameters between the right and left sides among bilateral cleft patients. Conclusions: The study highlights distinct TMJ morphological differences between growing and non-growing patients with CLP, emphasizing the importance of age-specific considerations in the treatment planning and growth monitoring of these patients. Full article

Incidental findings (IFs) depicted in imaging tests during the diagnostic evaluation of patients with cleft lip and/or palate (CL/P) can guide clinicians during treatment planning procedures for effective, comprehensive cleft care. Evidence regarding IFs in different anatomical regions distant from the dentition is scarce. The aim of this study was to compare the prevalence of IFs in various anatomical areas between patients with non-syndromic CL/P and unaffected subjects. Orthopantomographs (OPTs), lateral cephalometric (LC) radiographs, and cone beam computed tomography (CBCT) scans of 120 subjects (case group: n = 40, 18 females, age 14.5 ± 5.0 years; control group: n = 80, 36 females, age 14.6 ± 4.9 years) were examined, and IFs were assessed by four observers. A significantly higher prevalence of IFs (p < 0.001) was reported in the case group (97.5%) compared with the control group (62.5%). The most prevalent location of IFs in the case group was the maxilla (92.5%), followed by the nasal cavity (75.8%) and the mandible (63.2%), while in the control group, the highest rates of IFs occurred in the maxilla (43.8%), mandible (41.3%), and temporomandibular joint (TMJ) (14.7%). No gender-dependent pattern for IF occurrence was detected overall. Orofacial clefts may affect the mandible. However, the reported IFs were limited compared to those in the maxilla. In conclusion, individuals with CL/P are more likely to present with a range of IFs than their unaffected peers. Understanding the association between CL/P and IFs is critical for successful interdisciplinary treatment, raising awareness of the potential need for future dental care for cleft patients, and managing extra-dental aberrations. A systematic assessment of diagnostic records is required to eliminate the risk of overlooking clinically significant IFs. Full article

Orofacial clefts (OFCs) are the second most common birth defect worldwide. The etiology of OFCs involves complex interactions between genetics and environment. Advances in genomic technologies have identified gene variants associated with OFCs. This study aimed to investigate whether selected SNPs in the MYH9, MTHFR, MAFB, and SUMO1 genes influence the occurrence of non-syndromic OFCs in the Polish population. The study included 209 individuals with non-syndromic OFCs and 418 healthy controls. Saliva and umbilical cord blood samples were collected for DNA extraction. Four SNPs in the MYH9, MTHFR, MAFB, and SUMO1 genes were genotyped using real-time PCR-based TaqMan assays. Statistical analysis was performed using logistic regression to assess the association between SNPs and OFCs. A significant association was found between the rs7078 CC polymorphism and OFCs (OR = 3.22, CI 1.68–6.17, p < 0.001). No significant associations were identified for the rs1081131, rs13041247, and rs3769817 polymorphisms. The research indicates that the rs7078 polymorphism significantly influences the occurrence of orofacial cleft palate in the Polish population, whereas the rs3769817, rs1801131, and rs13041247 SNPs do not show such a correlation. Full article